The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform

Siufai Lui - One of the best experts on this subject based on the ideXlab platform.

  • common occurrence of an Antiidiotypic Antibody that recognizes t14 anti dna antibodies in patients with systemic lupus erythematosus
    Arthritis & Rheumatism, 1996
    Co-Authors: Pakleong Lim, Danny T M Leung, Kongchiu Wong, Siyang Song, Yiuloon Chui, Joseph Leung, K N Lai, Siufai Lui
    Abstract:

    Objective. To investigate whether antibodies to a T14 anti-DNA Antibody can be found in patients with systemic lupus erythematosus (SLE). Methods. Seventy-six serum samples (37 from patients with SLE) were randomly selected from among sera submitted for routine antinuclear Antibody testing. Short, overlapping peptides based on the partial VH (variable region of the heavy chain) sequence of the T14 Antibody were synthesized on multipins and screened for reactivity with SLE sera. In addition, selected peptides from T14 and related proteins were synthesized in bulk and screened for reactivity with both SLE and control sera. A monoclonal Antibody was generated to determine the prevalence of the T14 idiotype (T14+ Id) in the different study populations. Results. Antibodies were detected by a peptide based on the third complementarity-determining region (CDR3) of the T14 protein in 15 (41%) of 37 patients with SLE or 15 (54%) of 28 who had anti-DNA antibodies, in 3 (9%) of 34 patients without anti-DNA antibodies (9 of whom had SLE), and in 6 (10%) of 57 healthy controls. In SLE sera, the Antiidiotypic (anti-Id) responses (IgM and IgG) correlated well with the anti-DNA responses (IgG), and both responses correlated well with the T14+ Id activity in SLE sera. Control peptides based on the 18/2 (16/6+ Id) and S107 proteins detected low Antibody activities in SLE sera, attributable to cross-reactivity with the T14 peptide. A peptide based on an unrelated human Antibody was not reactive with these sera. Conclusion. Anti-Id antibodies directed to T14 VHCDR3 were found commonly in the sera of patients with SLE, and they appeared to be induced by the anti-DNA antibodies present in the sera. Based on these findings, these secondary antibodies may be pathogenic in SLE.

Luciano Polonelli - One of the best experts on this subject based on the ideXlab platform.

  • Engineered killer mimotopes: New synthetic peptides for antimicrobial therapy
    Current Medicinal Chemistry, 2004
    Co-Authors: Walter Magliani, Stefania Conti, R. Frazzi, Antonella Salati, Simona Arseni, Lara Ravanetti, Luciano Polonelli
    Abstract:

    This review deals with a novel approach to produce synthetic antibiotic peptides (killer mimotopes), similar to those described for the conversion of epitopes into peptide mimotopes, allowing their use as surrogate vaccines. Synthetic peptides pertaining to the complementary determining regions (CDRs) of a recombinant Antiidiotypic Antibody (PaKTscFv), which mimic the wide spectrum of microbicidal activity of a killer toxin produced by the yeast Pichia anomala (PaKT), have proven to act as structural or functional mimotopes of PaKT. This activity appeared to be mediated by interaction with specific cell wall killer toxin receptors (KTRs), mainly constituted by β glucans. Killer mimotopes have shown in vitro an impressive microbicidal activity against Candida albicans. They were adopted as a model of PaKT- and PaKTscFvsusceptible microorganisms. Optimization through alanine scanning led to the generation of an engineered decapeptide (KP) of a CDR-L1 pertaining Antibody fragment with an enhanced in vitro microbicidal activity. It had a potent therapeutic effect against experimental vaginal and systemic candidiasis in normal and immunodeficient mice caused by flucanozole susceptible and resistant yeast isolates. KP exerted a microbicidal activity in vitro against multidrug-resistant eukaryotic and prokaryotic pathogenic microorganisms, which was neutralized by interaction with laminarin (β 1,3-glucan). To our knowledge, KP represents the prototype of an engineered peptide fragment derived from a microbicidal recombinant Antiidiotypic Antibody. It is capable of exerting antimicrobial activity in vitro and a therapeutic effect in vivo presumably acting through interaction with the β glucan KTR component in the cell walls of pathogenic microorganisms.

  • therapeutic activity of an engineered synthetic killer Antiidiotypic Antibody fragment against experimental mucosal and systemic candidiasis
    Infection and Immunity, 2003
    Co-Authors: Luciano Polonelli, Walter Magliani, Stefania Conti, Luisa Bracci, Luisa Lozzi, Paolo Neri, Daniela Adriani, Flavia De Bernardis, Antonio Cassone
    Abstract:

    Peptides derived from the sequence of a single-chain, recombinant, Antiidiotypic Antibody (IdAb; KT-scFv) acting as a functional internal image of a microbicidal, wide-spectrum yeast killer toxin (KT) were synthesized and studied for their antimicrobial activity by using the KT-susceptible Candida albicans as model organism. A decapeptide containing the first three amino acids (SAS) of the light chain CDR1 was selected and optimized by alanine replacement of a single residue. This peptide exerted a strong candidacidal activity in vitro, with a 50% inhibitory concentration of 0.056 μM, and was therefore designated killer peptide (KP). Its activity was neutralized by laminarin, a β1-3 glucan molecule, but not by pustulan, a β1-6 glucan molecule. KP also competed with the binding of a KT-like monoclonal IdAb to germinating cells of the fungus. In a rat model of vaginal candidiasis, local, postchallenge administration of KP was efficacious in rapidly abating infections caused by fluconazole-susceptible or -resistant C. albicans strains. In systemic infection of BALB/c or SCID mice preinfected intravenously with a lethal fungal load, KP caused a highly significant prolongation of the median survival time, with >80% of the animals still surviving after >60 days, whereas >90% of control mice died within 3 to 5 days. KP is therefore the first engineered peptide derived from a recombinant IdAb retaining KT microbicidal activity, probably through the interaction with the β-glucan KT receptor on target microbial cells.

Stefania Conti - One of the best experts on this subject based on the ideXlab platform.

  • Engineered killer mimotopes: New synthetic peptides for antimicrobial therapy
    Current Medicinal Chemistry, 2004
    Co-Authors: Walter Magliani, Stefania Conti, R. Frazzi, Antonella Salati, Simona Arseni, Lara Ravanetti, Luciano Polonelli
    Abstract:

    This review deals with a novel approach to produce synthetic antibiotic peptides (killer mimotopes), similar to those described for the conversion of epitopes into peptide mimotopes, allowing their use as surrogate vaccines. Synthetic peptides pertaining to the complementary determining regions (CDRs) of a recombinant Antiidiotypic Antibody (PaKTscFv), which mimic the wide spectrum of microbicidal activity of a killer toxin produced by the yeast Pichia anomala (PaKT), have proven to act as structural or functional mimotopes of PaKT. This activity appeared to be mediated by interaction with specific cell wall killer toxin receptors (KTRs), mainly constituted by β glucans. Killer mimotopes have shown in vitro an impressive microbicidal activity against Candida albicans. They were adopted as a model of PaKT- and PaKTscFvsusceptible microorganisms. Optimization through alanine scanning led to the generation of an engineered decapeptide (KP) of a CDR-L1 pertaining Antibody fragment with an enhanced in vitro microbicidal activity. It had a potent therapeutic effect against experimental vaginal and systemic candidiasis in normal and immunodeficient mice caused by flucanozole susceptible and resistant yeast isolates. KP exerted a microbicidal activity in vitro against multidrug-resistant eukaryotic and prokaryotic pathogenic microorganisms, which was neutralized by interaction with laminarin (β 1,3-glucan). To our knowledge, KP represents the prototype of an engineered peptide fragment derived from a microbicidal recombinant Antiidiotypic Antibody. It is capable of exerting antimicrobial activity in vitro and a therapeutic effect in vivo presumably acting through interaction with the β glucan KTR component in the cell walls of pathogenic microorganisms.

  • therapeutic activity of an engineered synthetic killer Antiidiotypic Antibody fragment against experimental mucosal and systemic candidiasis
    Infection and Immunity, 2003
    Co-Authors: Luciano Polonelli, Walter Magliani, Stefania Conti, Luisa Bracci, Luisa Lozzi, Paolo Neri, Daniela Adriani, Flavia De Bernardis, Antonio Cassone
    Abstract:

    Peptides derived from the sequence of a single-chain, recombinant, Antiidiotypic Antibody (IdAb; KT-scFv) acting as a functional internal image of a microbicidal, wide-spectrum yeast killer toxin (KT) were synthesized and studied for their antimicrobial activity by using the KT-susceptible Candida albicans as model organism. A decapeptide containing the first three amino acids (SAS) of the light chain CDR1 was selected and optimized by alanine replacement of a single residue. This peptide exerted a strong candidacidal activity in vitro, with a 50% inhibitory concentration of 0.056 μM, and was therefore designated killer peptide (KP). Its activity was neutralized by laminarin, a β1-3 glucan molecule, but not by pustulan, a β1-6 glucan molecule. KP also competed with the binding of a KT-like monoclonal IdAb to germinating cells of the fungus. In a rat model of vaginal candidiasis, local, postchallenge administration of KP was efficacious in rapidly abating infections caused by fluconazole-susceptible or -resistant C. albicans strains. In systemic infection of BALB/c or SCID mice preinfected intravenously with a lethal fungal load, KP caused a highly significant prolongation of the median survival time, with >80% of the animals still surviving after >60 days, whereas >90% of control mice died within 3 to 5 days. KP is therefore the first engineered peptide derived from a recombinant IdAb retaining KT microbicidal activity, probably through the interaction with the β-glucan KT receptor on target microbial cells.

  • In vitro leishmanicidal activity of a monoclonal Antibody mimicking a yeast killer toxin.
    The Journal of eukaryotic microbiology, 2002
    Co-Authors: Dianella Savoia, Stefania Conti, Claudlo Avanzini, Valter Magliani, R. Frazzi, Uciano Polonelli
    Abstract:

    The microbicidal effect of a monoclonal Antiidiotypic Antibody, mimicking the activity of a yeast killer toxin, characterized by a wide antimicrobial spectrum, has been evaluated in vitro against two relevant species of protozoan parasites, Leishmania major and Leishmania infantum. The Antiidiotypic Antibody exerted a significant and dose-dependent antileishmanial activity against parasite promastigotes in comparison to an irrelevant isotype-matched monoclonal Antibody. This is the first demonstration that an Antibody, which had been already shown to be fungicidal and bactericidal, may also exert a direct microbicidal activity against protozoa.

Pakleong Lim - One of the best experts on this subject based on the ideXlab platform.

  • common occurrence of an Antiidiotypic Antibody that recognizes t14 anti dna antibodies in patients with systemic lupus erythematosus
    Arthritis & Rheumatism, 1996
    Co-Authors: Pakleong Lim, Danny T M Leung, Kongchiu Wong, Siyang Song, Yiuloon Chui, Joseph Leung, K N Lai, Siufai Lui
    Abstract:

    Objective. To investigate whether antibodies to a T14 anti-DNA Antibody can be found in patients with systemic lupus erythematosus (SLE). Methods. Seventy-six serum samples (37 from patients with SLE) were randomly selected from among sera submitted for routine antinuclear Antibody testing. Short, overlapping peptides based on the partial VH (variable region of the heavy chain) sequence of the T14 Antibody were synthesized on multipins and screened for reactivity with SLE sera. In addition, selected peptides from T14 and related proteins were synthesized in bulk and screened for reactivity with both SLE and control sera. A monoclonal Antibody was generated to determine the prevalence of the T14 idiotype (T14+ Id) in the different study populations. Results. Antibodies were detected by a peptide based on the third complementarity-determining region (CDR3) of the T14 protein in 15 (41%) of 37 patients with SLE or 15 (54%) of 28 who had anti-DNA antibodies, in 3 (9%) of 34 patients without anti-DNA antibodies (9 of whom had SLE), and in 6 (10%) of 57 healthy controls. In SLE sera, the Antiidiotypic (anti-Id) responses (IgM and IgG) correlated well with the anti-DNA responses (IgG), and both responses correlated well with the T14+ Id activity in SLE sera. Control peptides based on the 18/2 (16/6+ Id) and S107 proteins detected low Antibody activities in SLE sera, attributable to cross-reactivity with the T14 peptide. A peptide based on an unrelated human Antibody was not reactive with these sera. Conclusion. Anti-Id antibodies directed to T14 VHCDR3 were found commonly in the sera of patients with SLE, and they appeared to be induced by the anti-DNA antibodies present in the sera. Based on these findings, these secondary antibodies may be pathogenic in SLE.

Walter Magliani - One of the best experts on this subject based on the ideXlab platform.

  • Engineered killer mimotopes: New synthetic peptides for antimicrobial therapy
    Current Medicinal Chemistry, 2004
    Co-Authors: Walter Magliani, Stefania Conti, R. Frazzi, Antonella Salati, Simona Arseni, Lara Ravanetti, Luciano Polonelli
    Abstract:

    This review deals with a novel approach to produce synthetic antibiotic peptides (killer mimotopes), similar to those described for the conversion of epitopes into peptide mimotopes, allowing their use as surrogate vaccines. Synthetic peptides pertaining to the complementary determining regions (CDRs) of a recombinant Antiidiotypic Antibody (PaKTscFv), which mimic the wide spectrum of microbicidal activity of a killer toxin produced by the yeast Pichia anomala (PaKT), have proven to act as structural or functional mimotopes of PaKT. This activity appeared to be mediated by interaction with specific cell wall killer toxin receptors (KTRs), mainly constituted by β glucans. Killer mimotopes have shown in vitro an impressive microbicidal activity against Candida albicans. They were adopted as a model of PaKT- and PaKTscFvsusceptible microorganisms. Optimization through alanine scanning led to the generation of an engineered decapeptide (KP) of a CDR-L1 pertaining Antibody fragment with an enhanced in vitro microbicidal activity. It had a potent therapeutic effect against experimental vaginal and systemic candidiasis in normal and immunodeficient mice caused by flucanozole susceptible and resistant yeast isolates. KP exerted a microbicidal activity in vitro against multidrug-resistant eukaryotic and prokaryotic pathogenic microorganisms, which was neutralized by interaction with laminarin (β 1,3-glucan). To our knowledge, KP represents the prototype of an engineered peptide fragment derived from a microbicidal recombinant Antiidiotypic Antibody. It is capable of exerting antimicrobial activity in vitro and a therapeutic effect in vivo presumably acting through interaction with the β glucan KTR component in the cell walls of pathogenic microorganisms.

  • therapeutic activity of an engineered synthetic killer Antiidiotypic Antibody fragment against experimental mucosal and systemic candidiasis
    Infection and Immunity, 2003
    Co-Authors: Luciano Polonelli, Walter Magliani, Stefania Conti, Luisa Bracci, Luisa Lozzi, Paolo Neri, Daniela Adriani, Flavia De Bernardis, Antonio Cassone
    Abstract:

    Peptides derived from the sequence of a single-chain, recombinant, Antiidiotypic Antibody (IdAb; KT-scFv) acting as a functional internal image of a microbicidal, wide-spectrum yeast killer toxin (KT) were synthesized and studied for their antimicrobial activity by using the KT-susceptible Candida albicans as model organism. A decapeptide containing the first three amino acids (SAS) of the light chain CDR1 was selected and optimized by alanine replacement of a single residue. This peptide exerted a strong candidacidal activity in vitro, with a 50% inhibitory concentration of 0.056 μM, and was therefore designated killer peptide (KP). Its activity was neutralized by laminarin, a β1-3 glucan molecule, but not by pustulan, a β1-6 glucan molecule. KP also competed with the binding of a KT-like monoclonal IdAb to germinating cells of the fungus. In a rat model of vaginal candidiasis, local, postchallenge administration of KP was efficacious in rapidly abating infections caused by fluconazole-susceptible or -resistant C. albicans strains. In systemic infection of BALB/c or SCID mice preinfected intravenously with a lethal fungal load, KP caused a highly significant prolongation of the median survival time, with >80% of the animals still surviving after >60 days, whereas >90% of control mice died within 3 to 5 days. KP is therefore the first engineered peptide derived from a recombinant IdAb retaining KT microbicidal activity, probably through the interaction with the β-glucan KT receptor on target microbial cells.